title: Caffeic acid phenethyl ester downregulates phospholipase D1 via direct binding and inhibition of NFκB transactivation.
abstract: Upregulation of phospholipase D (PLD) is functionally linked with oncogenic signals and tumorigenesis. Caffeic acid phenethyl ester (CAPE) is an active compound of propolis extract that exhibits anti-proliferative, anti-inflammatory, anti-oxidant, and antineoplastic properties. In this study, we demonstrated that CAPE suppressed the expression of PLD1 at the transcriptional level via inhibition of binding of NFκB to PLD1 promoter. Moreover, CAPE, but not its analogs, bound to a Cys837 residue of PLD1 and inhibited enzymatic activity of PLD. CAPE also decreased activation of matrix metalloproteinases-2 induced by phosphatidic acid, a product of PLD activity. Ultimately, CAPE-induced downregulation of PLD1 suppressed invasion and proliferation of glioma cells. Taken together, the results of this study indicate that CAPE might contribute to anti-neoplastic effect by targeting PLD1.
authors.affiliation: Department of Molecular Biology, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Mi Hee
authors.initials: MH
authors.lastname: Park
authors.forename: Dong Woo
authors.initials: DW
authors.lastname: Kang
authors.forename: Yunjin
authors.initials: Y
authors.lastname: Jung
authors.forename: Kang-Yell
authors.initials: KY
authors.lastname: Choi
authors.forename: Do Sik
authors.initials: do S
authors.lastname: Min
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000201:enzymology* / Q000473:pathology; D002109:Caffeic Acids / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005910:Glioma / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D010739:Phospholipase D / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011429:Propolis / Q000737:chemistry; D015533:Transcriptional Activation / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D002109:Caffeic Acids; D016328:NF-kappa B; D011429:Propolis; D010739:Phospholipase D; C106801:phospholipase D1; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol
keywords: Caffeic acid phenethyl ester; Glioma cells; Invasion; Phospholipase D; Proliferation